Spirochetes are a medically significant but poorly understood group of bacteria. These organisms cause several important human diseases, such as syphilis, Lyme disease and leptospirosis. Spirochetes are very diverse, but they share a special attribute: Spirochetes can swim in a highly viscous, gel-like medium, such as that found in connective tissue, that inhibits the motility of most other motile bacteria. It is believed that the motility and chemotaxis are very important virulence factors in the pathogenic spirochetes. However, the basic biology of motility and chemotaxis and their roles in the process of the diseases are poorly understood due to the paucity of genetic tools and the fastidious growth of spirochetes. The spirochete Borrelia burgdorferi (Bb) is the causative agent of Lyme disease, which is the most prevalent tick-borne disease in the Unites States. In addition to being an important clinical entity, Bb is one of the best understood spirochetes and one for which genetic tools have rapidly evolved in the past few years. The goal of this proposal is to utilize Bb as a genetic model to elucidate the unique aspects of spirochete motility and chemotaxis, as well as their roles in the process of the disease. To achieve this goal, this proposal focuses on the following specific aims: (1) To elucidate the molecular mechanisms involved in the unique aspects of spirochete motility and chemotaxis by using Bb as a genetic model. (2) To determine the roles of motility and chemotaxis in the infection processes of Bb. The results obtained from this study will lead to better understanding the basic biology of spirochete motility and chemotaxis, as well as their roles in the processes of the disease, which could eventually lead to new means for the prevention and treatment of the disease (e.g., developing vaccines or inhibitors that target the key elements of Bb motility and chemotaxis). The pathogenic spirochetes, such as the Lyme disease spirochete Borrelia burgdorferi, are highly motile and invasive. The goal of this project is to understand the basic biology of spirochete motility and chemotaxis, and their roles in the pathogenesis of the diseases. The obtained results may lead to new means of disease prevention and treatment.